Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). METHODS: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. RESULTS: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. CONCLUSIONS: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.

Prevalence of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease.

OBJECTIVE: End-stage chronic liver disease is associated with accelerated ageing and increased frailty. Frailty measures have provided clinical utility in identifying patients at increased risk of poor health outcomes, including those awaiting liver transplantation. However, there is limited data on the prevalence and severity of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of frailty and prefrailty in patients with non-cirrhotic NAFLD and correlate with severity of liver disease. DESIGN: A cross-sectional analysis of functional and laboratory frailty assessments, including the Fried frailty index (FFI), a self-reported frailty index (SRFI) and a lab-based frailty index (FI-LAB), was performed in a cohort of 109 patients with NAFLD, and results compared with fibrosis staging based on transient elastography. RESULTS: Patients with NAFLD had a high prevalence of prefrailty and frailty, with a median SRFI score of 0.18 (IQR: 0.18), FFI of 1 (IQR: 1) and FI-LAB of 0.18 (IQR: 0.12). Using the SRFI, 45% of F0/F1 patients were classified as prefrail and 20% were classified as frail, while in F2/F3 patients this increased to 36% and 41%, respectively. SRFI, 30 s sit-to-stand and FI-LAB scores increased with increasing liver fibrosis stages (p=0.001, 0.006 and <0.001, respectively). On multivariate linear regression, female gender was identified as a significant predictor of elevated frailty scores. CONCLUSION: This study identifies a high prevalence of frailty in individuals with non-cirrhotic NAFLD. Addressing frailty through early rehabilitation interventions may reduce overall morbidity and mortality in this population.

Digital tools to support the maintenance of physical activity in people with long-term conditions: A scoping review.

Objective: This scoping review aimed to bring together and identify digital tools that support people with one or more long-term conditions to maintain physical activity and describe their components and theoretical underpinnings. Methods: Searches were conducted in Cumulative Index to Nursing and Allied Health Literature, Medline, EMBASE, IEEE Xplore, PsycINFO, Scopus, Google Scholar and clinical trial databases, for studies published between 2009 and 2019, across a range of long-term conditions. Screening and data extraction was undertaken by two independent reviewers and the Preferred Reporting Items for Scoping Reviews guidelines informed the review's conduct and reporting. Results: A total of 38 results were identified from 34 studies, with the majority randomised controlled trials or protocols, with cardiovascular disease, type 2 diabetes mellitus and obesity the most common long-term conditions. Comorbidities were reported in >50% of studies but did not clearly inform intervention development. Most digital tools were web-browser-based ± wearables/trackers, telerehabilitation tools or gaming devices/components. Mobile device applications and combination short message service/activity trackers/wearables were also identified. Most interventions were supported by a facilitator, often for goal setting/feedback and/or monitoring. Physical activity maintenance outcomes were mostly reported at 9 months or 3 months post-intervention, while theoretical underpinnings were commonly social cognitive theory, the transtheoretical model and the theory of planned behaviour. Conclusions: This review mapped the literature on a wide range of digital tools and long-term conditions. It identified the increasing use of digital tools, in combination with human support, to help people with long-term conditions, to maintain physical activity, commonly for under a year post-intervention. Clear gaps were the lack of digital tools for multimorbid long-term conditions, longer-term follow-ups, understanding participant's experiences and informs future questions around effectiveness.

Exercising in the COVID-19 era: implications in non-alcoholic fatty liver disease (NAFLD).

COVID-19 is a major public health pandemic. Risk factors for severe infection and poorer outcomes include cardiovascular disease, obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Lifestyle interventions, including diet and physical activity modifications, are the current recommended treatment for NAFLD. In this communication, the authors discuss the crossover link between NAFLD and severe COVID-19 infection and the impact of essential public health measures to suppress the spread of COVID-19 on exercise and physical activity participation in patients with NAFLD. The future of exercise prescription and the potential use of digital technology in addressing NAFLD healthcare needs in the COVID-19 era are also explored.

A systematic review of physical activity in people with haemophilia and its relationship with bleeding phenotype and treatment regimen.

INTRODUCTION: Although the measurement of physical activity (PA) amongst people with haemophilia (PWH) has become increasingly widespread in recent years, the relationship between PA and bleeding phenotype remains poorly understood. In addition, the influence of various treatment regimens on this relationship has not been defined. AIM: This review aimed to systematically assess the data that are available regarding PA levels amongst PWH, as well as the relationship between PA and bleeding. METHODS: A systematic search of the online databases EMBASE, Cochrane, MEDLINE Ovid, CINAHL and Web of Science was conducted by two independent reviewers. Quality assessment was undertaken using the AXIS Critical Appraisal Tool for Cross-sectional Studies and the STROBE checklist. RESULTS: Of 1902 sources identified overall, 36 articles were included. Low-to-moderate transparency of reporting and various sources of bias were identified. PA levels varied amongst heterogeneous samples of PWH. The relationship between PA and bleeds was inconclusive, although there was evidence that improvements in treatment over recent decades have appeared to enable PWH to become more physically active. CONCLUSION: Based upon the limited available evidence, the relationship between PA and bleeding phenotype in PWH remains unclear. However, with the development of improved prophylaxis treatment regimens in recent years, there is evidence that PA levels have increased, especially amongst people with severe haemophilia. The use of validated outcome measures of PA and more robust reporting of bleeds and treatment regimen are warranted in future research, especially in a rapidly evolving era of new treatments for PWH.

Determinants of Physical Activity Engagement in Patients With Nonalcoholic Fatty Liver Disease: The Need for an Individualized Approach to Lifestyle Interventions.

OBJECTIVES: Physical activity (PA) is an important non-pharmacological treatment for non-alcoholic fatty liver disease (NAFLD). This study investigated the determinants of PA engagement and awareness of the World Health Organization (WHO) PA guidelines in patients with NAFLD. METHODS: Study participants were 101 patients with NAFLD (median age: 54 [IQR = 15] y; 53 men and 48 women) who completed 4 questionnaires: (1) a PA guideline awareness questionnaire; (2) a PA questionnaire assessing PA levels; and (3) 2 questionnaires assessing perceived barriers and motivators for engaging in PA. Binary logistic regression was performed to assess predictors of PA levels. RESULTS: Twenty-four percent of participants correctly identified the recommended WHO weekly PA guidelines, and 39% adhered to the guidelines. Lack of willpower, time, and energy were the most frequently cited barrier domains. Scores for lack of willpower (odds ratio [OR] = 1.445, 95% CI = 1.088-1.919) and lack of resources (OR = 1.378, 95% CI = 1.003-1.893), and reporting 3 or more "significant" barrier domains (OR = 5.348, 95% CI = 1.792-15.873) were significant predictors of PA levels. Maintaining health and fitness was the most cited motivator domain and was a significant predictor (OR = 2.551, 95% CI = 1.253-5.208) of PA levels. CONCLUSIONS: This study highlights the lack of awareness of the WHO PA guidelines and the key determinants of PA participation in patients with NAFLD. Determinants of PA should be identified at the individual level to create a personalized approach for PA maintenance for people with NAFLD to promote lifelong participation in PA. IMPACT: This study closes a gap in the published data on the determinants of PA engagement in patients with NAFLD. LAY SUMMARY: Physical inactivity is the fourth leading cause of global mortality and contributes to many chronic inflammatory diseases, including obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). People with NAFLD engage in less physical activity compared with people who are healthy, and this study provides new information that clinicians can use to help these patients increase their physical activity participation.

Improvement in cognitive impairment following a 12-week aerobic exercise intervention in individuals with non-cirrhotic chronic hepatitis C.

Cognitive impairment occurs in 30%-50% of patients with non-cirrhotic chronic hepatitis C virus (HCV) infection. Exercise is beneficial in preventing and treating cognitive impairment and cardiometabolic abnormalities in many chronic inflammatory diseases, but there are few studies investigating the impact of exercise in HCV infection. The study aimed to assess the effect of a 12-week aerobic exercise intervention on cognition and extrahepatic manifestations in individuals with HCV. In this nonrandomized controlled pilot study, individuals with HCV participated in a 12-week aerobic exercise intervention. Outcome measures included cognition (Montreal Cognitive Assessment [MOCA], Trail Making Test A & B [TMT-A; TMT-B], Digit Symbol Test [DST]), cardiorespiratory fitness (estimated V˙O2max ), physical activity (accelerometry), anthropometry, quality of life (depression; fatigue; sleep quality) and biochemical markers. Outcomes were assessed at baseline (T0), intervention completion (T1) and 12 weeks after intervention completion (T2). Thirty-one patients completed the study (exercise group n = 13, control group n = 18). In the exercise group, cognition improved at T1 in the TMT-A (31% mean improvement, p = 0.019), TMT-B (15% mean improvement, p = 0.012) time and MOCA (14% mean improvement, p ≤ 0.001). These improvements were not maintained at T2. Depression (p = 0.038), sleep quality (p = 0.002), fatigue (p = 0.037) and estimated V˙O2max (7.8 mL kg-1  min-1 [22%] mean increase, p = 0.004) also improved at T1. In conclusion, this study demonstrates the benefits of a 12-week aerobic exercise intervention in improving cognition, quality of life and cardiorespiratory fitness in individuals with HCV. Larger studies are needed to confirm these findings and strategies for continued exercise engagement in individuals with HCV are warranted for sustained benefits.

Improvement in histological endpoints of MAFLD following a 12-week aerobic exercise intervention.

BACKGROUND: Lifestyle interventions are the primary treatment for metabolic (dysfunction) associated fatty liver disease (MAFLD). However, the histological and cardiometabolic effects of aerobic exercise in MAFLD remain unclear. AIMS: To assess the effects of a 12-week aerobic exercise intervention on histological and cardiometabolic endpoints in MAFLD. METHODS: Patients with biopsy-confirmed MAFLD participated in a 12-week aerobic exercise intervention. Liver histology, cardiorespiratory fitness (estimated V̇O2max ), physical activity, anthropometry and biochemical markers were assessed at baseline, intervention completion, and 12 and 52 weeks after intervention completion. RESULTS: Twenty-four patients completed the exercise intervention (exercise group n = 16, control group n = 8). In the exercise group, 12 weeks of aerobic exercise reduced fibrosis and hepatocyte ballooning by one stage in 58% (P = 0.034) and 67% (P = 0.020) of patients, with no changes in steatosis (P = 1.000), lobular inflammation (P = 0.739) or NAFLD activity score (P = 0.172). Estimated V̇O2max increased by 17% compared to the control group (P = 0.027) but this level of improvement was not maintained at 12 or 52 weeks after the intervention. Patients with fibrosis and ballooning improvement increased estimated V̇O2max by 25% (P = 0.020) and 26% (P = 0.010), respectively. Anthropometric reductions including body mass (P = 0.038), waist circumference (P = 0.015) and fat mass (P = 0.007) were also observed, but no patient achieved 7%-10% weight loss. CONCLUSION: This study highlights the potential benefits of a 12-week aerobic exercise intervention in improving histological endpoints of MAFLD. The development of strategies to ensure continued engagement in aerobic exercise in MAFLD are needed.